Cycloaliphatic unsaturated ketones as odour- and taste-modifying agents

ABSTRACT

New cycloaliphatic unsaturated ketones and their use as perfuming and odour-modifying agents in the manufacture of perfumes and perfumed products, and as flavouring and tastemodifying agents in the preparation of foodstuffs in general and imitation flavours for foodstuffs, beverages, animal feeds, pharmaceutical preparations and tobacco products. Methods for the preparation of said cycloaliphatic unsaturated ketones.

United States Patent 1191 Kovats et al.

[73] Assignee: Finnenich S.A., Geneva,

Switzerland [22] Filed: Sept. 6, 1974 [2]] Appl. No.: 503,794

Related U.S. Application Data [60] Division of Ser. No. 35,594, May 7, l970, abandoned, which is a continuation-in-part of Ser. No. 774,|79, Nov. 7, I968, abandoned.

[] Foreign Application Priority Data Nov. 9, 1967 Switzerland l5667/67 Nov. 1, 1968 Switzerland 16309/68 May 7, 1969 Switzerland 6976/69 Aug. 8, I969 Switzerland 12065/69 Apr. 14, I970 Switzerland 5559/70 Apr. 17, 1970 Switzerland 5725/70 [52] US. Cl 260/586 R; 131/17; 252/522;

260/348 R; 260/348 C; 260/469; 260/488 R;

[ Dec. 23, 1975 260/488 H; 260/514 J; 260/530 N; 260/544 L; 260/546; 260/586 C; 260/586 F; 260/586 P; 260/595; 260/598; 260/] R; 260/6l7 R; 260/617 E; 260/6l7 F; 260/632 Y; 260/638 R; 260/638 Y; 260/642; 260/666 R; 426/155;

[51] Int. Cl C07C 49/61 [58] Field of Search 260/586 R [56] References Cited OTHER PUBLICATIONS Demole et al., Helv. Chim. Acta.," Vol. 53, Fasc. 3(1970) PP. 541-551.

Primary Examiner-Norman Morgenstern Attorney, Agent, or FirmPennie & Edmonds [57] ABSTRACT New cycloaliphatic unsaturated ketones and their use as perfuming and odour-modifying agents in the manufacture of perfumes and perfumed products, and as flavouring and taste-modifying agents in the preparation of foodstuffs in general and imitation flavours for foodstuffs, beverages, animal feeds, pharmaceutical preparations and tobacco products.

Methods for the preparation of said cycloaliphatic unsaturated ketones.

5 13 Claims, No Drawings CYCLOALIPI-IATIC UNSATURATED KETONES AS ODOUR- AND TASTE-MODIFYING AGENTS This is a division of application Ser. No. 35,594 filed May 7, 1970, which in turn is a continuation-in-part of application Ser. No. 774,179, filed Nov. 7, 1968 both now abandoned.

SUMMARY OF THE INVENTION The invention relates to a new class of cycloaliphatic unsaturated ketones having the formula containing one double bond in position 2- or 3' of the acyl side-chain and either one double bond in position I- or 2-(as shown in the above formula, the double bond in the 2 position can be either in the cycle or the side chain), or two conjugated double bonds in positions land 3- of the cycle, the double bonds being represented by dotted lines, and wherein n is zero or 1, R, R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen, and R, R, R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen.

The invention also relates to methods for the preparation of compounds I, of some of the intermediates used in their preparation and some of their derivatives and to the use of said compounds as perfuming and odour-modifying agents in the manufacture of perfumes and perfumed products, and as flavouring and taste-modifying agents in the manufacture of artificial flavours for foodstuffs, beverages, animal feeds, pharmaceuticals and tobacco.

DESCRIPTION OF THE PREFERRED EMBODIMENTS The compounds of the invention have particularly interesting and valuable organoleptic properties and, consequently, they are useful as fragrances in the perfume industry, as ingredients for the preparation of artificial flavours and as flavour additives in foodstuffs, animal feeds, beverages, pharmaceutical preparations and tobacco products.

The term foodstuff is used in this specification in its broadest sense and is meant to include also products such as coffee, tea and cocoa. In particular, the new ketones and some of their intermediates can be used as odoriferous ingredients in concentrated or diluted perfumes and in perfumed products such asoaps. detergents. cosmetic products, wa-es and any other products which may be perfumed to make them commer cially more attractive.

Furthermore, the new compounds are very useful as ingredients" in the preparation of artificial essential oils such .l. ,asmin oil, geranium Bourbon oil, rose oil and iihfil':

The compounds of the invention increase the power and the diffusion ability of perfume compositions and impart to them a natural richness.

The compounds of the invention possess also very interesting flavouring properties. Depending on the nature of the products to which they are added, they will develop fruity, herb-like, winy, woody, floral or waxy flavour notes or any combinations of these flavour notes. In some instances they will impart to products a red berry-like flavour and can be used for improving the taste and aroma of artificial strawberry, cranberry, cherry or redcurrant flavour compositions and the like. Surprisingly, the new ketones can even be used for enhancing the taste and flavour of such products as honey and red wines.

The proportions in which the new compounds can be used to produce desirable odoriferous effects vary within wide limits. In the preparation of perfume compositions, for instance, interesting effects can be obtained with proportions as low as about ppm to about 5% of the total weight ofa perfume composition. Depending on the odoriferous effects wanted, the proportions of the ketones can be increased to about 10% or even more.

When the new ketones are used as flavouring agents or additives for modifying the organoleptic properties of foodstuffs, animal feeds, beverages, pharmaceutical preparations and tobacco products, the new compounds can be used in proportions which, again, vary within wide limits.

Interesting flavouring effects, for instance, can be achieved by using the compounds of the invention in proportions from 0.1 to 10 ppm based on the weight of the products to be flavoured. However, these proportions can be increased beyond 10 ppm up to about 100 ppm in order to achieve special flavouring effects. In the proparation of flavouring compositions by admixing the new compounds to other aromatics, the said componds can be used, for example, in proportions of about 0.l% to about 15% of the total weight of the flavouring composition. In many cases average proportions of about 1 to l0% by weight will give the desired results.

It is to be understood that the proportions given above are in no way absolute values and that higher or lower concentrations of the new compounds may be used depending on the specific odoriferous or flavouring effects to be developed.

According to the invention, the methods of preparation of the compounds of formula I are either of general nature or of more specific type.

According to the invention, a general method for the preparation of compounds of formula containing either one double bond in position lor 2- or two conjugated double bonds in positions land 3- of the cycle, the double bonds being represented by COX IV a, B, r

a endocyclic double bond in position 2 B endocyclic double bond in position 1- y exocyclic double bond in position 2- wherein the dotted lines and the symbols R, R R and R have the same meaning as above and wherein the symbol X represents a leaving group such as halogen, O-alkyl, O-aryl, O-CO-aryl, O-CO-alkyl.

A preferred mode of operation consists in using, as cyclogeranoyl derivatives, geranoyl halogenides such as, for instance, chlorides, bromides or iodides or geraniate derivatives such as methyl, ethyl or lithium geraniate. The cyclogeranoyl and safranyl derivatives used in the above mentioned process can be synthesized according to different methods, some of which are described hereinafter. For instance,

1. The cyclogeranoyl derivatives of structure aand B- can be synthesized from the corresponding cyclogeranic acids by usual methods. The cyclogeranic acids may be obtained from the corresponding citral derivatives according to known methods [ef.: Gildemeister &-Hoffman, Die Aetherischen Oele, lll d. pp. l37l38, Akademie-Verlag, Berlin 0966)]. The process for the preparation of the cyclogeranoyl derivatives of structure aand [3- can be illustrated by the following scheme A wherein the dotted lines and the symbols R have the same meaning as above.

Scheme i I o:-cidat;ic n

citral derivatives T b -continued OOH cyelisation geranic acid derivatives halogenation 03 2. The cyclogeranoyll derivatives of structure a,

B- can also be obtained by cyclisation of the corresponding citral derivatives [e.g. cf.: Bedoultian, Perfumery and Flavoring Synthetics, Elsevier, New York (1967)], whereas the cyclogeranoyl derivatives of structure 7- are obtained by isomerization of B-cyclocitrals. The aldehydic group of cyclocitrals is oxidised to -COOl-l and finally this latter is transformed into COX by the usual means. Scheme B illustrates this process. The dotted lines and the symbols R have the same meaning as above.

a-cycloeitrals OOH 3. The cyclogeranoyl derivatives of structure -y, 60 where X= O-alkyl, can be prepared according to Helv. Chim. Acta 41, I359 (1958) from an aalkoxycarbonyl derivative of cyclohexanone. By

condensation of these derivatives with an ethyl 65 6 R 3 CH0 R B-cyclocitrals A j someri-zahbn -cyclocitrals W Iv Y" haloacetate in the presence of zinc a diester is obtained which, after dehydration, partial saponification and monodecarboxylation, gives the desired y-compounds. This process is illustrated in Scheme C hereinafter. The dotted lines and the symbols R have the same meaning as above.

S erherie C R 7 7 R COX 6 6 cox 6 B OX R R g cox D H llalCH -COOEt 5 Zn l R R c at lon h i y 1 C06. u cooizt R R dct-rlfbs'J xylaki on The a-alkoxycarbonyl derivatives of cyclohexanone may be obtained according to Helv. Chim. Acta 35, I753 1952 from methylheptenone. 2 1

- 6 (O-CH c -c R 4. The safranyl derivatives used In the process of the R A/ present invention can be obtained simply by dehyl drogenating the corresponding B-cyclogeranoyl x derivatives as follows. The substltuents R have the 5 same meaning as above. n

l I Y- The dehydrogenation may be carried out in the same way as that described for one of the process of the invention which consists in converting compound la, and [B into 15. This process will be described hereafter (see p. 23).

According to the invention. a method for the prepzrration of ketones of formula containing one double bond in position 2'- or 3'- of the acyl side-chain and one double bond in position I- (structure [3-) or 2- (structure 04-, endocyclic double bond; structure exoc yclic double bond) of the cycle, the double bonds being represented by dotted lines, and wherein n is zero or 1, R, R and R represent hydrogen or one of them a lower alkyl radical such as methyl or ethyl, and the others hydrogen, and R", R R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen, comprises oxidising an alcohol of formula I I 2 3 l CHOll*CH- C C R n 2-n 7 n R l I v T wherein the dotted lines and the symbols R have the same meaning as those of formula 1. Silver carbonate in presence of diatomaceous earth, oxygen-containing derivatives of a transition element such as chromium, manganese or nickel, pure or atmospheric gaseous oxygen in presence of activators, such as, for example free radicals initiators, can be used as oxidising agents. Chromium trioxide and manganese dioxide are preferably used [see for example, J. Org. Chem. 26, 4814 (i961 )1. MnO is a cheap oxidising agent which can be used at room temperature in an inert solvent such as pentane and hexane.

When it is used to convert V to I, the geometric isomerism of the material being oxidised (cisor transalcohols V or mixture thereof) remains practically unchanged. When C20 is used, preferably in the presence of an organic base such as pyridine, the ketone resulting from either the cis-.or trans-alcohols V has the geometry trans-. The starting compounds V which possess interesting organoleptic properties and, consequently, can be advantageously used in the perfume industry, can be prepared according to usual methods by the addition to 01-, B- or 'y-cyclocitrals of an organometallic derivative having the formula containing one double bond in position I" or 2'-, the double bond being represented by the dotted lines, and

Scheme F nr b 40 wherein ME represents a metallic function such as, for instance, Li or BrMg, R, R and R have the same meaning as above and n is zero or I, and subsequent hydrolysis of the addition product.

5 The above process is illustrated by scheme E herebelow, wherein the dotted lines and the symbols R have the same meaning as above.

The 01-, B- and y-cyclocitrals can be prepared from citral derivatives as indicated in scheme B (see above) and schemes F and G will illustrate a few examples of reactions for the preparation of such starting citral derivatives. in these schemes the symbols R have the same meaning as indicated above, ME represents a ME J pr f n 0 5 Scheme C:

b. Carrol reaction [see for example J. Chem. Soc. pp.

c: Reactions for the conversion of methylheptenones to the corresponding citrals [see for example Bedoukian, Perfumery and Flavoring synthetics,

Elsevier, New York (1967), p. 102-103] methylheptenone derivakive The alcohol of formula I I R R2 R5 cno citral derivative V Y-a 1 3 14 wherein the symbol R represents hydrogen, R and R Bedoukian, Perfumery and Flavoring synthetics Elrepresent hydrogen or one of them a lower alkyl radisevier, New York (1967)]. cal, such as methyl or ethyl, and the other hydrogen. When cyclising agents such as proton acids are used and R R R and R have the same meaning as above, to effect the cyclisation the resulting ketone l possesses can be prepared by isomerisation and simultaneous generally the structure-B, that is to say with the double reduction of an epoxide having the formula bond in the ring conjugated with the CO-group (posil 3 xvr t wherein the R's have the same meaning as above [sec tion lof the ring). When cyclising agents such as Tetrahedron l9, 1091 (l963) and J. Org. Chem. 26, Lewis acids are used in the cylisation, for instance 36l5 (1961 boron trifluoroetherate or SnCl the resulting ketone l According to the invention, the ketones of formula 1 possesses generally the structure 01-, that is to say with aand I 3-, wherein the double bond of the acyl sidethe double bond in position 2- of the ring. The cyclisachain is in position 2'-, are prepared by cyclising, by tion is preferably carried out by means of SnCl in an means of an acidic cyclising agent, a "pseudo-ketone ine t Sol ent Such as benzene of o e Qf formula In the above mentioned process. the starting pseu- 7 do"-ketones, which are new odoriferous compounds R and can be advantageously used in the perfume indus- 5 1 try, can be easily obtained by reacting, a citral deriva- R -C' ==C --CH R tive (see scheme G) with an organo-metallic derivative I I 1 of propene (see formula III above) under conditions R analogous to those described for the preparation of 5 alcohols V and subsequent oxidation of the resulting I alcohol with an oxidising agent. Said oxidation can be VI carried out by means of the same oxidising agents and R under reaction conditions analogous to those used for wherein the R's ahave the same meaning as in formula the oxldatlo" of alcohols havmg formula I. The cyclisation can be carried out under the same 40 p eud0"-ket0nes VI can also be prepared from conditions used for cyclising the l,5-dieno compounds, methylheptenone derivatives Schemfi according for example for cyclising citral to cyclocitral or geranic t0 the process shown in scheme H hereinbelow wherein acid to cyclogeranic acid [see for example, P. Z. the symbols R have the same meaning as above.

Scheme H:

. R 7 R 6 K R T ethynylation 5 i on DalxyL-MgBr 1 2)R CH=CR CHXR cucl /x X Halogen Table -continued OAc CuAc

l l R According to the invention a method for the preparation of compounds having the formula containing one double bond in position 1- or 2- of the cycle, the double bonds being represented by dotted lines, wherein R R and R represent hydrogen or R a lower alkyl radical, such as methyl or ethyl, and the others hydrogen, and R R R and R represent hydrogen or one of them a lower alkyl radical, suchas methyl or ethyl, and the others hydrogen, comprises partially hydrogenating the triple bond of an acetylenic ketone having the formula VII wherein the dotted lines and the symbols R have the same meaning as in formula I. The partial hydrogenation can be performed in the presence of a Lindlar type catalyst (deactivated Pd/C catalyst, see Helv. Chim. Acta 35, 446 (1952)) according to usual methods. The ketones l a-a and l B-a resulting from the above partial hydrogenation have the configuration cis-. The corresponding transisomers are prepared according to the invention by isomerisation with an acid in an inert solvent. Acids which can be used for carrying out the above isomerisation comprise proton acids, such as those ordinarily used to produce enolisation of ketones, for instance p-toluenesulfonic acid, hydrochloric acid and trifluoracetic acid. Lewis acids, such as for instance boron trifluoride or iodine, can also be used. The isomerisation is best carried out in an inert solvent such as an aromatic hydrocarbon, for example benzene or toluene, an aliphatic or cycloaliphatic hydrocarbon, e.g. heptane or cyclohexane or an ether, e.g. monoglyme, diglyme or dioxan. The temperature at which the isomerisation can be carried out is not critical. For instance, the isomerisation can be carried out by mixing the substance to be isomerised together with the solvent and a catalytic amount of the acidic isomerising agent and allowing the mixture to stand at room temperature for several hours, e.g. 12 hours. At lower temperature the reaction time may increase considerably. At temperatures higher than the room temperature the reaction time may be shortened. However, above 100 C unwanted side reactions may occur and it is preferable to carry out the isomerisation below 100 C.

The acetylenic ketones VI] which are used as starting V to ketones I can be under similar conditions. Good results are obtained by carrying out the oxidation with MnO in a cheap inert solvent such acylation, hexane, cyclohexane or petroleum ether.

. 5 materials m the above process are themselves odolfer- The acetylenic ketones f f l v" can l b Gus hew compounds which can be used in the Perfume prepared by the direct actylation, according to usual 'y- P0Ssess Valuable floral fragrances They procedures, of organo-metallic propyne derivatives of can be prepared by a method which comprises reacting formma aor B-cyclocitrals with organo-metallic derivatives of 10 CH pmpyne Sub5eq em|y hydrolymng, h macho prod wherein ME represents a metallic function such as for ucts to acetylemc alcohols and oxidising the latter to instance Li, Na or K with cyclogeranoyl derivatives the ketones having the formula IV aor IV [3- (see scheme A above).

This method can be Illustrated by scheme I under- 15 According to the invention a method for the prepa neath ration of compounds having the formula l n'e-c c-cn a 2 l In scheme the dotted lines and the symbols R have the same meaning as above. The symbol ME represents a metal function such as those commonly found in organo-metallic compounds, for instance alkali metals, mercury, zinc, cadmium and magnesium. In case where ME represents a divalent metal, i.e. for instance Mg, the second valence bond can be linked to a negative substituent such as for instance Br, C1 or I. For the oxidation of the acetylenic alcohols to ketones VII, the same oxidising agents used for the oxidation of alcohols oxidation 1 u-a, B-a

containing one double bond in position 1- or 2- of the cycle, the double bond being represented by dotted lines, wherein R, R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen, and R R R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen, comprises isomerising compounds having the formula wherein the dotted lines and the symbols R have the same meaning as above, by means of an acidic or basic isomerising agent or by means of heat. An acidic isomerising agent a strong mineral or organic acid, such as for instance sulphuric acid, phosphoric acid, gaseous hydrochloric acid, perchloric acid, p-toluensulfonic acid and trifluoracetic acid can be used. p-Toluensulfonic acid is preferably used. The isomerization by means of an acidic isomerising agent can be carried out in an organic solvent. For instance, most of the commonly used organic solvents such as aliphatic cycloaliphatic hydrocarbons, aromatic hydrocarbons, chlorinate hydrocarbons or esters and ethers can be conveniently used. Benzene is preferably used.

As basic isomerising agent an alkali, an alkali-buffer or an organic base can be used.

According to the invention a method for the preparation of compounds having the formula CO-CH C CH R n I 2-n R R 20 R7 2' 3| 6 CO-CH C "'CH R R l W m l a R 11. 101-, B-

l R l 0-b, B-b

wherein the dotted lines and the symbols R have the same meaning as above.

The dehydrogenation can be carried out by halogenating the cyclohexenic ring in the allylic position and subsequently dehydrohalogenating the product of halogenation. As halogenating agents, commonly known halogenating reactants of the allylic position such as for instance, haloamides, for example N-bromosuccinimide, N-bromoacetamide, N-dimethyldibromohydantoin and their chlorinated analogues can be used.

According to the usual procedure, N-bromosuccinimide is preferably used [see Chem. Rev. 63, 2t (1963)].

The halogenation in the allylic position can be carried out in an inert solvent at a mild temperature. For instance, a chlorinated solvent such as CCl CHCl CH Cl dichloroethane, tetrachloroethane and trichloroethylene or a mixture of said solvents and temperature between about 20 and 100 can be considered as convenient. It is possible to operate at higher temperatures, but the course of the reaction becomes difficult to follow. Preferably, the allylic halogenation is carried out in a mixture of CCl, and Cl-l Cl or CHCl at a temperature comprised between 40 and C.

The presence in the reaction mixture of an initiator such as a-a'-azo-bis-isobutyronitrile or benzoyl peroxide or the use of actinic radiations is advantageous. In such case in fact, the initial reaction temperature can be appreciably lower than in the absence of such an initiator; an easier control of the course of the reaction is thus possible.

The dehydrohalogenation of the resulting halogenated product of the above reaction can be carried out without isolation and/or previous purification of said halogenated product and can be promoted by organic bases such as for instance tertiary amines. As tertiary amines piperidine, morpholine, tributylamine, diethylaniline and dimethylaniline can be used. Preferably, diethylaniline is used owing to its low volatility but other tertiary amines can be equally effective.

The temperature of the dehydrolhalogenation is comprised between 100 and 150 C. However, it is possible to operate at temperatures below or above these limits but at temperatures below 100 C the reac tion time may become longer, whereas at temperatures above 150 C the product may undergo a partial decomposition.

According to the invention a method for the preparation of compounds having the formula wherein R R and R represent hydrogen or one of them a lower alkyl radical, such as methyl or ethyl, and the others hydrogen and R, R R and R represent hydrogen or one of them a lower alakyl radical, such as methyl or ethyl, and the others hydrogen, comprises treating with an acidic agent an epoxy-compound of formula containing one double bond in position 2'- or 3- of the acyl side-chain, the double bond being represented by dotted lines, wherein n is zero or 1, and wherein the oxygen atoms of the epoxide cycle is bound to the positions 1- and 2- or 2- and 3- of the cycle and the symbols R have the same meaning as above.

As acidic agents, mineral or organic acids such as, for instance, hydrochloric acid, phosphoric acid, sulphuric acid, p-toluensulfonic acid and trifluoroacetic acid or acidic diatomaceous earth can be used. The reaction can be carried out in an organic solvent such as for example benzene, toluene, tetrahydrofuran, dioxan or ethyl acetate at a temperature comprised between about and about 100 C. Preferably, phosphoric acid in dioxan or tetrahydrofuran is used and the reaction is carried out at the boiling temperature of said solvents.

The above reaction proceeds through the formation of an hydroxy intermediate of formula containing one double bond in position 2'- or 3'- of the acyl side-chain and one double bond in position 1- or 2- of the cycle, the double bonds being represented by dotted lines, wherein n is zero or 1 and wherein the symbols R have the same meaning as in formula l6-a.

As oxidising agent, an oxygen containing derivative of an alkali metals, such as potassium chromate or bichromate, or of a transition element, such as chrome, manganese or nickel, can be used, The oxidation is preferably carried out by CrO in a mineral or organic acid.

The oxidation of compounds Vii to ketones IB-a can also be carried out by the successive use of at least two different oxidising agents such as, for instance, a peracid and CrO According to a preferred mode of operation, a peracid in a buffered hydrophobic solvent and an acid aqueous solution of CrO are added successively to the alcohol Vii at room temperature. In this process a peracid such peracetic acid, (performic) acid, perbenzoic acid, (perphtalic) acid or mchloroperbenzoic acid in a solvent such as, for instance, chloroform, methylene chloride, benzene or trichloroethylene in the presence of a buffer such as an alkali acetate, can be used. Preferably, CrO is then used in an aqueous solution acidified with H 80 The above method can be summarised by scheme J hereinafter.

Solmmvi 1 CHCH;;.:-'C '-CH, R I n n oxidant; V11 3 2 VIII ii 6 co-cn c---c R R n 2-n' H K R R 5 L. VIII 5.

6 co-c-:. c CH a R 2 J R A 5 In the above scheme J the dotted lines, the index n and these epoxides, which are new odoriferous products the symbols R have the same meaning as in formula 50 VIIli (see above).

According [0 the above described process the epoxy flavour Industry, are prepared accordlng to the Invenintermediates are not isolated; however, when required tion by epoxidising a compound of formula and can be advantageously used in the perfume and ii) x 1-H wherein the dotted lines, the index n and the symbols R have the same meaning as above and X represents an oxygen or hydrogen and an OH group. As epoxidising agents the same peracids described above for the oxidation of V ii can be used. The reaction can be carried out in an analogous way.

The epoxy-ketones VIII i are obtained according to the invention by oxidation of compound VIII ii.

As oxidising agents, the reactants commonly known to oxidise a secondary hydroxylic function to a ketonic function such as oxygen-containing derivatives of silver or of a transition element such as chrome, manganese or nickel, can be conveniently used.

An alkali bichromate in acidic solution is preferably used.

The compounds of general formula I possess in their side-chain a cisor transconfiguration. Some of the methods of the invention give generally mixtures in which the respective amounts of the two isomers vary within broad limits. As a general rule, for economic reasons the mixtures obtained by one of the above process are used in the perfume industry without further purification or separation. However, if necessary the two isomeric forms can be separated by the usual methods, for instance, by column or vapour phase chromatography. Moreover, cis-isomers isomerise to the corresponding trans-isomers in the presence of acids. By actinic radiations an equilibrium is established between the two forms, in other words, by irradiating one or the other of the two isomers, a mixture, in which the amount ratio of the two isomers is constant, will be formed. Such ratio will not change even if the radiation time is protracted.

It has been found that bicyclic compounds of formula l 2 R l/ R R f cn a XII and

XIV

R XI

containing one double bond in position 2'- or 3'- of the acyl side-chain and containing either one double bond in position I- or two conjugated double bends in positions 1- and 3- of the cycle, the double bonds being represented by the dotted lines, and wherein the index n is zero or 1 and the symbols R have the same meaning as in formula X i.

The cyclisation can be carried out by using as acidic agent either a mineral or organic protonic acid, such as hydrochloric acid, phosphoric acid, sulphuric acid, acidic diatomaceous earth, p-toluenesulfonic acid or trifluoracetic acid, or Lewis acids, such as BP AlCl SnCL, or iodine. It is possible to cyclise the compounds of formula XI to compounds X i by dissolving the compounds to be cyclised in the presence of the acidic agent in an inert organic solvent. Most of the solvents commonly used, such as aliphatic, cycloaliphatic or aromatic hydrocarbons or esters and ethers can be conveniently used. Preferably, acidic diatomaceous earth in dioxan or tetrahydrofuran is used.

As basic agents strong inorganic bases, such as hydroxy-derivatives of alkali metals, for example lithium, sodium or potassium hydroxides, or organic bases, such as primary, secondary or tertiary amines, for example diethylamine, triethylamine, n-propylamine, di-npropylamine, tri-n-propylamine, n-butylamine, aniline, methylaniline, dimethylaniline, trimethylamine or diethylamine, can be used. In addition, said cyclisation can be carried out by means of usual nucleophilic reagents such as, for example, I, or 8 0 The bicyclic ketone of formula is also prepared by oxidising the corresponding carbinol having the formula CH-CO-Cll XVI a according to a procedure analogous to that followed for converting XVI into V 'ya [see above, cf. Tetrahedron 19, I091 (1963) and J. Org. Chem. 26, 3615 (l96l )1.

According to another method of the invention, compounds of formula XII are prepared by cyclising by means of an acidic or basic agent compounds having the formula containing one double bond in position 2'- or 3'- of the acyl side-chain, the double bond being represented by a dotted line, and wherein the symbols R have the same meaning as in formula XII and the index n is zero or 1.

The above cyclisation can be carried out by using the same type of acidic or basic reagents as those mentioned for converting compounds XI to their corresponding bicyclic derivatives X i. Preferably, there is used, as cyclising agent, BE, in an inert organic solvent such as, for example, benzene, toluene or ether, or a mixture thereof.

The present invention describes also a method for the preparation of cyclic ketones of formula XIV which comprises cyclising by means of heat compounds of formula wherein the symbols R have the same meaning as in formula XIV.

The reaction can be carried out in inert organic solvents such as, for example, those already mentioned for the cyclisation of compounds XI or XIII. The temperature to which said cyclisation can occur is not critical. It is preferable to operate at a temperature comprised between l00 and At lower temperatures the reaction times can be considerably longer. At temperatures higher than those indicated the reaction time can be shorter: however, at these temperatures fragmentation reactions can occur.

Specific examples of compounds comprised by the various structural formulae shown hereinbefore include 2 ,4,6,6-tetramethyll -trans-crotonoyl l -cyclohexene,

2 ,4,6,6-tetramethyl-l-[ l-hydroxy-2-butenyl1-I- cyclohexene,

2 ,4,6,6-tetramethyl-l -trans-crotonoyl-l ,3-cyclohexadiene,

2 ,5 ,6,6-tetramethyll -trans-crotonoyl-l -cyclohexene,

2 ,5 ,6,6'tetramethyl-l-[ l-hydroxy-2-butenyl1-lcyclohexene,

2 ,5,6,6-tetramethyll -trans-crotonoyl-1 ,3-cyclohexadiene,

2 ,5,6,6-tetramethyll 3-methyl-2-butenoyl1-l cyclohexene,

2,6,6-trimethyll l -hydroxy-3-methyl-2-butenyl]-l cyclohexene,

2,6,6-trimethyl-l 3-methyl-2-butenoyl1- l 'cyclohexene,

2,6,6-trimethyl-l -[3-methyl-2-butenoyl ]-l ,3-

cyclohexadiene,

2,3,6,6-tetramethyll -crotonoyl-2-cyclohexene,

2,3,6,6-tetramethyll l-hydroxy-2-butenyl1-2- cyclohexene,

2,6,6-trimethyl-1-vinylacetyl-l-cyclohexene,

2,6,6-trimethyll 3-methyl-3-butenoyl1-l -cyclohexene,

2 ,6,6-trimethyl- 1 Z-pentenoyl ]-2-cyclohexene,

7 ,1 l-dimethyl-S-oxo-3,6,lO-dodecatriene,

2,6,6-trimethyl-l Z-methylcrotonoyll-Z-cyclohexene,

2,6,6-trimethyll B-methylcrotonoyl ]-2-cyclohexene,

2,6,6-trimethyll -crotonoyl-l ,2-epoxycyclohexane,

2,6,6-trimethyll -vinylacetyl-l ,Z-epoxycyclohexane,

2,6,6-trimethyl-l-[ l-hydroxy-3-butenyl1-l -cyclohexene,

2,6,6-trimethyl-l l-hydroxy-3-butenyl1-l ,2-epoxycyclohexane,

2,6,6-trimethyll l-hydroxy-2-butenyl1-l ,2-epoxycyclohexane,

2,6,6-trimethyl-l l-hydroxy-3-butenyll-2-cyclohexene,

2,6,6-trimethyll -vinylacetyl-Z-cyclohexene,

5,6,6'trimethyl-2-methylene-l-[3-methyl-3- butenoyl]-cyclohexane,

cisand trans-5,6,6-trimethyl-2-methylene-l-[Z-pentenoyll-cyclohexane,

cisand trans-5,6,6-trimethyl-2methylene-1- crotonoylcyclohexane,

cisand trans-6-ethyl-6-methyl-2-methylene-l-[2- methyl-2-butenoyl]-cyclohexane,

6-ethyl-6-methyl-2methylenel-[3-methyl-2- butenoyllcyclohexane,

cisand trans-6-ethyl-6-methyI-Z-methylene-1-[2- pentenoyllcyclohexane.

cisand trans 6-ethyl-dmethyl-Z-methylene-lcrotonoylcyclohexane.

cisand trans-6,6-dimethyl-lmethylene-l-[2-methy1-2butenoyl]cyclohexane.

6,6-dimethyl-2methylene-l-[3-methyl-2-butenoyl]- cyclohexane,

cisand trans-6,6-dimethyl-2 methylene-l-(2-pentenoyll-cyclohexane,

2,6,6-trimethyl-l-[3-methyl-3-butenoylJ-Z-cyclohexene and cis' and trans-2,6-dimethyl-6 -etliyl-l crotonoyl1- cyclohexene.

The invention will be illustrated in a more detailed manner by the following Examples. in said Examples temperatures are given in degreees centrigrade.

EXAMPLE 1 2 ,4,6 ,6-Tetramethyll -trans-crotonoyl 1 -cyclohexene A mixture of 10 g. of 2,4,6,6-tetramethyl-l-[ lhydroxy-Z-butenyll-l-cyclohexene. prepared according to paragraphe f) hereinafter, 100 g. of activated MnO and 300 ml. of pentane was stirred at 20 in an atmosphere of argon during 45 h. After filtration the solid was washed with pentane and the clear filtrate was brought to dryness. The residue obtained from the above operation was dissolved in 100 ml. of dry ben zene, added of 160 mg. of p-toluensulfonic acid and allowed to react at room temperature in argon atmosphere during 16 h. By extracting with ether in the presence of NaHCO (5 solution) and collecting the organic layers, 7.96 g. (80 of 2,4,6,6-tetramethyl-ltrans-crotonoyl-l-cyclohexene were obtained after distillation in vacuo. B. p. 60-210.00l Torr. Purification by column chromatography (H sio benzene) gave a pure sample; the analytical data were as follows: d, 0.9223; n 1.4919; I.R.:v=970 (CH=CH- trans), 1615, 1645, 1670 cm (C=C, C=O); Mass spectrum: M 206; NMR.: 0.80-1.05 (6 H, m, 2 CH 1.09 (3 H, s, CH -C 1.48 (3 H, s, CH -C=), 1.88 (3 H, dd, .1 6.5 and ca. 1 cps, CH=CHCH 1.2-2.2 H, m). 6.00 (l H, d. q.,.l= 16 and ca. 1 cps, COCl;l=CH-CH 6.63 (1 H, d. q., .l 16 and 6.5 cps. CO-CH=Cfl-CH UV.: 11 225 nm (e*' 12,390)

C H O Caled C 81.50 H 10.75 7r Found C 81.49 H 10.89

2,4,6,6'Tetramethy1- l l-hydroxyQ-butenyll-l cyclohexene used as starting material in the above preparation can be obtained as follows:

a. 4-Methyl-3-penten-2-ol according to He1v.Chim. Acta 30. 2216 (1947).

Mesityl oxide (245 g.) dissolved in 1200 ml. of dry ether was added at reflux temperature to a mixture of LiAlH (30 g.) in 200 ml. of the same solvent (1 h.). The mixture was allowed to react at during 2 h. and after decomposition of the excess of LiAlH by means of wet ether, it was added to a solution of 200 g. of NH Cl in 1 l. of water.

After extraction with ether, the usual treatments gave 221 g. (88 of 4-methyl-3-penten-2-ol; B.p. 4750/ll Torr. The product thus obtained was wet and it was conveniently dried by treatment with anhydrous K CO in pet.ether (30-50). d 0.8421; n 1.4388;

[R1 v= 1050 (C-O), 1670 (C=C), 3350 cm (OH) MS.: M 100 NMR.: 1.11 (3 H, d,.l=6cps), 1.64 (6 H,m), 4.04 (l 4.15-4.65 (1 H, m), 5.10 (l H, cl, J=ca. 8 cps). Sppm.

C H O Cal. ed: C 71.95; H 12.08 Found C 71.83; H 12.19

b. 4-Bromo-2 methyl-2 pentene according to Helv.

Chim. Acta 30, 2216 (1947).

4-Methyl-3-penten-2-ol (220 g.) in 250 ml. of pet.- ether (3050) and dry pyridine (41 g.) was added to a solution of freshly distilled PBr (233 g.) and 10 drops of dry pyridine at 20 (1 h.). The reaction mixture was directly distilled and 274 g. (76 of 4-bromo-2-methyl-2-pentene were obtained. Owing to its instability, the product must be employed without too long storage.

c. 4,6-Dimethyl-S-heptene-2one according to. Helv. Chim. Acta 30, 2216 (1947).

The bromide (274 g), obtained according to paragraph b) hereinabove. was added at a temperature comprised between -5 and l0 to acetylacetate (obtained from 40.7 g. of sodium and 230 g. of ethyl acety lacetate) in 670 m1. of anhydrous ethanol. The reaction mixture was allowed to react during 2 days at 20 and, after the usual treatments of extraction and drying, 252 g. of the ketoester intermediate were obtained. This substance was dissolved in 928 ml. of ethanol, added to a solution of Ba(OH) 8 H 0 (444 g in 3280 ml. of water), and kept to reflux during 2 h.

The precipitate which was formed during the above operation was dissolved with 10 HCl, extracted with ether and subjected to the usual treatments.

142 g. of product having B.p. 53-7/10 Torr were obtained. 70 of this product was constituted by 4,6-dimethyl-5-hepten-2-one and 30 by the allylic isomer.

The separation by means of preparative v.p.c. gave the two products which showed the following analytical data: 4,6-dimethyl-5-hepten-2-one 1R.: v 830, 1360 (CH CO), 1710 cm (CO) MS.: M" 140 NMR.: 0.89 (3 H,d, J 6.5 cps), 1.62 (6 H, s), 2.00 (3 H, s), 2.22 (2 H, d, J 7 cps), 2.5-3.2 (1 H, m), 4.83 (1 H, d,.l =8 cps) Sppm. 4,4-dimethyl 5-hepten-2-one NMR.: 1.07 (6 H,s), 1.63 (3 H,d,.l=4.5 cps), 1.99 (3 H, s), 2.28 (2 H, s), 5.40 (2 H, m) 8 ppm.

The mixture of these two isomers can be used as such in the following step. It must be noted that the rearranged structure will be eliminated during the successive cyclisation reaction (see paragraph e).

d. 2,4,6-Trimethyl-2,6-octadienal according to Tetrahedron Suppl. No. 8, Part 1, 347 1966).

Diisopropylamine (44.8 g.) in ml. dry ether was added in an atmosphere of argon to a solution of butyllithium (14 in hexane) in 200 ml. of dry ether and the mixture was then allowed to react at 20 during 2 h.

55 g. of ethylidencyclohexylamine were then added to the above mixture at followed by the addition at 70 of 70 g. of the ketones obtained according to paragraph c) above. The reaction mixture was left at 70 during 1% h., then at 20 during one night. After addition of 800 ml. of 20 acetic acid at 0, stirring during 3 h. at 20 in an atmosphere of argon and extrac tion followed by the usual treatments, three fractions were obtained.

Fraction 1: B.p. 3052/0.01 Torr; 4.6 g.

Fraction II: B.p. 52-70/0.5 Torr; 44.6 g. (53 Fraction 111: B.p. 7080/0.01 Torr; 5.1 g.

Residue 17 g.

Fraction 11 was redistilled and analysed by NMR. It was constituted by a mixture (ca. 3:2) of two isomeric aldehydes: 2,4,6-trimethyl-2,6-octadienal and 4,4,6- trimethyl-2,6-octadienal. This mixture was used for the next step.

e. 4-Methyl-B-cyclocitral A mixture of the two isomeric aldehydes obtained according to paragraph d) (36.5 g.), aniline (21.4 g.) and anhydrous sodium sulphate (20 g.) in 55 ml. of ether was left at 20 under stirring during one night. After having filtered, washed and concentrated to the initial volume the solution was poured with vigorous stirring into 221 ml. of cone. H 50 and 22.1 g. of ice. The temperature was kept between -20 and 25during 1 hr., and the mixture was then added to 300 g. of ice and immediately distilled by means of steam distillation. The distillate was saturated with NaCl, extracted with ether and treated as usual. 36 g. of a mixture of crude aand B- cyclocitral were thus obtained. The subsequent isomerisation was carried out at 10 in 120 ml. ofa 8.5 ethanolic KOH solution (80 ethanol). The mixture was allowed to react during 3 h. in an atmosphere of argon, diluted then with pet.-ether (3050), poured into 400 ml. of a NaCl saturated aqueous solution and finally extracted with peL-ether. By distillation 4-methyl-B -cyclocitral was obtained: Fraction 1: B.p. 30-73/10 Torr; 1.4 g.

Fraction II: B.p. 9095/l0 Torr; 18.6 g. (51 Residue 6 g.

1R: v 1610, 1670, 1720 (C=C; C=O), 2760, 2820 cm (CHO) MS: M 166 NMR: 0.92 (3 H, d, J ca. 4 cps), 1.13 (6 H, s), 2.05 (3 H, s), 1.0-2.30 H, m), 10.22 (1 H, s) 8 ppm. UV: h 248 (5 9416) C H O Cal.ed C 79.46; H 10.92 Found C 79.39; H 10.86.

f. 2,4,6,6-Tetramethyl-1-[ l-hydroxy-2-butenyl1-1- cyclohexene A solution of 16.4 g. of 4-methyl-fi-cyclocitral obtained according to paragraph e) in 20 ml. dry ether was added (35 min.) at 20 to a solution of propenyl lithium. This latter solution was freshly prepared by adding at 10 a solution of 9.7 g. of l-chloropropene in 80 ml. of dry ether to 1.85 g. of granulated lithium containing 1 of sodium. After being left 3 h. at this lithium salt solution was ready for the addition of citral as described above.

After complete addition, the reaction was allowed to react at l5/-20 during 5 h., left at 20 during one night and poured then into 60 g. of NH C1 in water/ice. The reaction mixture was then extracted with ether and the ethereal combined extracts were concentrated at 40-50 in vacuo, the product is thermolabile. Fraction 1: B.p. 55/0.00l Torr, 0.5 g.

Fraction lll: B.p. 558/0.001 Torr, 18.6 g. (90

Fraction 11 represents 2,4,6,6-tetramethyl-l-[l- 34 hydroxy-2-butenyl]-l-cyclohexene in a cisand transmixture. df 0.9300; n 1.4933 IR: v 970 (CH=CH-trans), 1030 (CO), 1645 (C=C), 3400 cm (OH) MS: M 208 NMR: 0.8-1.2 (9 H, m), 15-18 (6 H, m), 1.0-2.3 (5H, m), 2.4 (l H, s, wide band), 4.65 (l H, m), 5.55 (2 H, m) 8 ppm.

C H O CaLed C 80.71; H 11.61 Found C 80.71; H 11.48

EXAMPLE 2 2,4,6,6-Tetramethyll -trans-crotonoyl-l ,3-cyclohexadiene 2,4,6,6-Tetramethyl-1-trans-crotonoyl-1-cyclohexene (4.86 g.) obtained according to Example 1, was stirred at 50 with N-bromosuccinimide (5.85 g.), bisazo-isobutyronitrile (0.6 mg. 40 ml. ofCH Cl and 40 ml. of CCl, in a moisture-free vessel. After 50 min. the solution became clear due to the solution of NBS and succinimide precipitated. The mixture was stirred 5 min. more at 50 then, after cooling at 20, diethylamine (10.6 g.) was added to it with stirring. After addition of 100 ml. of pet-ether (3050), homogenization and filtration, the filtrate gave by evaporation (at 40 under vacuum) and subsequent heating at |35-145 during one hour, 3.60 g. of a mixture 45:55 of the initial ketone and the final product. These two compounds were separated by v.p.c. (Carbowax 15 200, 2.5 m.).

2,4,6,6-Tetramethyl-transl -crotonoyl-l ,3-cyclohexadiene can also be separated by column chromatogra phy (40 parts by weight SiO in the presence of benzene). d 0.943, n 1.5115

IR: v 970 (-CH=CHtrans), 16204670 cm" (C=C, C=O) MS: M 204 NMR: 1.00 (6 H, s), 1.60 (3 H, s), 1.89 (3 H, d.d., J 6.5 and ca. 1 cps), 1.80 (3 H, s), ca. 1.7-1.9 (2 H, m), 5.52 (1 H,swide), 6.05 (1 H,d.q., .1 =16 and ca. 1 cps), 6.72 (l H, d.q.,.| 16 and 6.5 cps) '0 ppm.

UV: A f 227 mn (8= 15,090)

C H O Cal. ed C 82.30; H 9.87 Found C 82.43; H 10.09.

EXAMPLE 3 2 ,5 ,6,6-Tetramethyl- 1 -trans-crotonoyl- 1 -cyclohexene A mixture of 8.0 g. of 2,5,6,6-tetramethyl-l-|1- hydroxy-Z-butenyl]-l-cyclohexene, prepared according to paragraph e) hereinafter, g. of activated MnO, and 250 ml of pentane was stirred at 20 in an atmosphere of argon during 21 h. After filtration the solid was thoroughly washed with pcntane and the clear filtrate was brought to dryness. The residue thus obtained (8 g), which was constituted by 81 7a of the desired ketone, 16 of its cis-isomer and 3 7o impurity (v.p.c. Carbowax l5 200, 2.5 m), was dissolved in 80 ml. of dry benzene, added of mg. of p-toluenesulfonic acid and allowed to react at room temperature in an atmosphere of argon during 16 h. by extracting with ether in the presence of NaHCO (5 solution) and collecting the organic layers, 6.83 g. (86 of 2,5 ,6,6-tetramethyll -trans-crotonoyl- 1 -cyclohexane were obtained by vacuum distillation, B.p. 64-7/0.001 Torr.

IR: 970, 1615, 1640, 1670 cm" MS: M 206 NMR:O.8-1.0 9 H, m); 1.47 3 H, s); 1.87 3 H, d.d., J 6.5 and ca. 1 cps); 6.58 (l H, d.q., =16 and 6.5 cps) 8 ppm.

UV: A 227 m1 (6 11,545)

C H O Cal.ed C 81.50; H 10.75 Found C8127; H 10.46

2,5,6,6-Tetramethyl-l-[1-hydroxy-2-butenyl1-lcyclohexene used as starting material in the above preparation can be obtained as follows:

a. lBromo-2,3-dimethyl-2-butene according to Helv. Chim. Acta 23, 964 (1940).

Hydrobromic acid (600 g., 30 in acetic acid) was added under stirring to dimethylbutadiene (200 g.) at a temperature comprised between -25 and 15 during 1.5 h. After having been left 2 days at room temperature, the mixture was poured into ice-water and extracted with ether. The organic layer after the usual treatments gave two fractions:

Fraction 1: B.p. 3040/10 Torr, 60 g.

Fraction II: B.p. 42-4/10 Torr, 261 g. (72 of the desired product.

Residue, 50 g.

b. 5,6-Dimethyl-5-hepten-2-one according to Helv. Chim. Acta 23, 964 (1940).

The bromide (261 g.), obtained according to paragraph a) hereinabove, was added at 610 to acetyl acetate (obtained from 38.8 g. of sodium and 219 g. of ethylacetacetate) in 600 ml of anhydrous ethanol. The reaction mixture was allowed to react during one night at 20 and at reflux during 1.5 h. After dilution with five-fold its volume of water and the usual treatments of extraction and drying, 263 g. (77 of the ketoester intermediate were obtained. The distillation gave also a fraction with B.p. 30-42/0.001 Torr, 35 g., and a residue of 0.5 g.

The ketoester was dissolved in 960 ml. of ethanol, added to a solution of Ba(OH .8H O (460 g. in 3400 ml. of water) and kept boiling during 22 h.

The precipitate which was formed during the above operation was dissolved with 10 HCl, extracted with ether and subjected to the usual treatments.

144 g. (83 of a product having B.p. 70-1/10 Torr were obtained. Together with this product a fraction having B.p. 69/10 Torr and a residue of 3.0 g. were obtained.

5,6Dimethyl-5 hepten-2-one shows the following analytical constants:

IR: v 1350,1710 cm"- MS: M 140 NMR: 1.63 (9 H, s), 2.07 (3 H, s); 2.30 (4 H, m) 5 PP" C H O Calc.ed C 77.09; H 11.50 Found C 77.11; H 11.69

c. 3,6,7Trimethyl-Z,fi-octadienal according to Tetrahedron Suppl. No. 8, Part I, 347 (1966) Methyl iodide (79.8 g.) in 250 ml. of dry ether was added at to a suspension of lithium (7.77 g) and 150 ml. of dry ether and the mixture was then allowed to react at during 24 h.

Diisopropylamine (55.7 g.) in 100 ml. dry ether was added to the above mixture and left to react at 20 during 2 h.

68.7 g. of ethylidencyclohexylamine [see Bull. Soc. Chim. France 1947, 715) were added, followed by the addition at -70 of 70 g. of dimethylheptenone.

After the same treatment described in Example 1, paragraph d, 2 fractions were obtained:

Fraction 1: B.p. 3053/0.001 Torr; 4.5 g.

Fraction II: B.p. 53-656910.001 Torr; 46.1 g. (55 Residue 28 g.

Fraction II is a mixture ca. 1:2 of cisand trans-b 3,6,7-trimethyl-2,6-octadienal which can be separated by v.p.c. (Carbowax, 15 200, 2.5 m.).

The mixture showed the following data:

IR: v= 1630, 1660, 1715 (C=C), C=O), 2730,2860 cm (CHO) MS: M 166 NMR: 1.62 (9 H, s), 1.8-2.7 (7 H, complex band), 5.67 (1 H, d, .l= 7.5 cps), 10.05 (1 H, almost 1, .1 7.5 cps, due to mixing of two d) 8 ppm.

C H O Cal.ed C 79.46; H 10.92 Found C 79.21; H 10.80.

(1. S-Methyl-B-cyclocitral A mixture of the two isomeric aldehydes obtained according to paragraph c) (38 g.), aniline (22.3 g.) and anhydrous sodium sulphate (20 g.) in 23 ml. of ether was treated as described in Example 1, paragraph e), using 230 ml. of cone. H 50, and 23 g. of ice.

After steam distillation, saturation with NaCl and extraction 32 g. (84 of a 2:3 mixture of S-methyla-and 5-methyl-Bcyclocitrals were obtained. The subsequent isomerisation was carried out at -10 in 120 ml. of a 8.5 ethanolic KOH solution ethanol). By the treatment described in Example 2, e) 27.6 g. (86 of a product with B.p. 4854/0.001 Torr were obtained. This product consists of 3-4 of the aand 96-7 of the B-isomer.

IR: v= 1610, 1670, 1710, 2760, 2860 cm MS: M 166 NMR: 0.89 (3 H, m); 1.03 (3 H, s); 1.18 (3 H, s); 2.08 (3 H, s); 1.2-2.4 (5 H, m); 10.27 (1 H, s) 8 ppm.

UV:A, 248 mn (e 10,546)

C H O Calc.ed C79.46; H 10.92

Found C 79.43; H 10.80

e. 2,5 ,6,6-Tetramethyl-1-[ l-hydroxy-Z-butenyll- 1 cyclohexene A solution of 16.6 g. of S-methyl-B-cyclocitral obtained according to paragraph d) hereabove in 20 ml. dry ether was added (35 min.) at 20 to a solution of propenyl lithium. This solution was freshly prepared according to Example 1, paragraphf). The same treatment gave by distillation three fractions:

Fraction I: B.p. 40-56/0.001 Torr, 1.5 g.

Fraction II: B.p. 576210.001 Torr, 1.3 g.

Fraction Ill: B.p. 64-7/0.00l Torr, 9.9 g. (47.5 of the desired product.

IR: v 970, 1670, 3400 cm.

MS: M 208 NMR: 0.8-0.9 (3 H, m);0.95 (6 H,s); 1.0-2.2 12 H, m); 4.80 (l H, s); 5.70 (2 H, m) 8 ppm.

C H O Calc.ed C 80.71; H 11.61

Found C 80.83; H 11.54

EXAMPLE 4 2,5 ,6,6-Tetramethyl-l trans-crotonoyl- 1 ,3-cyclohe xadiene 2 ,5 ,6,6-Tetramethyl-1trans-crotonoyl-lcyclohexene (486g), obtained according to Example 3, was allowed to react, according to the same procedure described in Example 2 for the preparation of the corresponding 2,4,6,6-tetramethyl derivative with N- bromosuccinimide (5.85 g.) bis-azo-isobutyronitrile (0.6 mg), 40 ml. of CH CI and 40 ml. of CCl.,. By the usual treatment 3.71 g. (77 of a product at B.p. 75/0.001 Torr were obtained.

IR: v 970, 1610, 1630, 1670 cm.

MS: M" 204 NMR; 0.89 (3 H, s); 1.02 (3 H, s); 0.97 (3 H, d, J= ca. 8 cps); 1.58 (3 H, s 1.88 (3 H, d. d., J 6.5 and ca. 1 cps); 18-23 (1 H, m); 5.60 (2 H, m); 6.0 (1 H, d.q., J 16 and ca. 1 cps); 6.70 (1 H, d.q., J 16 and 6.5 cps) 8 ppm.

UV: A 228 m1; (e 11,640).

EXAMPLE 2,5 ,6,6-Tetramethyl- 1 -[3-methyl-2-butenoyl]-1 cyclohexene S-methyl-B-cyclocitral (11.0 g.) [of Example 3, paragraph d)] in 30 ml. THF was added at to a Grignard solution obtained from 2.4 g. of magnesium and 13.5 g. of 1-brom0-2-methyl-propene in 30 ml. of dry tetrahydrofurane.

The reaction mixture was allowed to react during 2h. at 5-0 and brought then at room temperature during one night.

The usual treatment with NH Cl at 0 and extraction gave:

Fraction 1; B.p. 40/0.00l Torr; 1.3 g.

Fraction ll: B.p. 70-2/0.00l Torr; 8.7 g. (59 of the desired product.

Residue: 4 g.

1R:v 1020, 3400 cm MS:M 222 NMR:0.65-1.10(9 H, m); 1.6-2.0 (9 H); 2,45 (1 H, s); 1.0-2.2 (5 H, m); 4.9 (1 H, almost d,j=ca. 8 8cps); 5.50 (1 H, almost d, J ca. 8 cps) 6 ppm.

The alcohol obtained above (6.4 g.) with Mn0 (64 g.) in 190 ml. of pentane was left at 20 during 42 h. in an atmosphere of argon. The usual treatment [c.f. Example 1] gave 5.3 g. of crude product. Two column chromatography runs, on 40 parts by weight of H 510 and 24 parts by weight of H SiO- respectively, enabled to obtain pure 2,5,6,6-tetra-methyl-1-[3-methyl-2- butenoyl]-1-cyclohexene.

B.p. 80/0.001 Torr; d 0.9353; n 1.5040

IR: 11 1605,1665 cm MS: M 220 NMR: 0.80-1.10 (9 H, m); 1.53 (3 H,s)', 2.14 (3 H, s); 1.39 (3H,s)', 1.3-2.3 (5 H, m); 6.06 (1 H, s) 8 ppm.

C, H .,O Calc.ed C 81.76; H 10.98

Found C 81.47; H, 10.87.

EXAMPLE 6 2,6,6-Trimethyl-1-[1-hydroxy-3-methyl-Z-butenyl]-1- cyclohexene A solution of 1-chloro-2-methyl-propene (47.5 g.) in 50 ml. of dry ether was added at 10 (A h) to a suspension of granulated lithium (7.6 g., containing 1% of sodium, in 50 ml of dry ether) in an argon atmosphere.

The reaction mixture was allowed to react at room temperature during 3 h., then B-cyclocitral (63 g.) was added to it at After 5 more hours at that temperature the mixture was kept overnight at poured into 38 a ice-cold aqueous solution of NH CI and finally extracted with ether.

After evaporation of the ether in vacuo at a temperature below 40-50 (the product is thermolabile 76 g. of crude alcohol were obtained. By careful distillation in the presence of traces of Na CO two fractions were obtained:

Fraction 1: B. p. 4755/0.00l Torr, 16.1 g.

Fraction II: B. p. 55-6010.001 Torr, 21.4 g. (24.8 of the desired product.

Fraction [1 solidified by cooling and was recrystallised with pet-ether (3050) at 10.

1R11020, 1650, 3400-3600 cm.

NMR:0.87 (3 H, s), 1.13 (3 H, s), 1.70-1.80 (9 H, m), 1.20 2.30 (6 H, m), 3.27 (1 H, s), 4.85 (1 H, d, J 8cps), 5.46 (1 H, almost (1, J 8 cps) 8 ppm.

C H O Calced C 80.71; H 11.61

Found C 80.65; H 11.54

EXAMPLE 7 2,6,6Trimethyl-1-[3-methyl-2-butenoyl]-cyclohexene 2,6,6-Trimethyll l-hydroxy-3-methyl-2-butenyl l-cyclohexene, prepared according to Example 6, 1.0 g.) with activated MnO (10 g.) in 30 ml. of pentane was mixed at room temperature during 63 h. After filtration and distillation 630 mg. (63 of the desired ketone, B.p. 67/0.001 Torr, were obtained.

1R: F1605, 1665 cm.

NMR'. 1.04 (6 H, s), 1.55 (3 H, s), 1.89 (3 H, d, J ca. 1 cps), 2.15 (3 H, s), 1.20-2.20 (6 H, m), 6.09 (l H, s) 8 ppm.

UVzA 244 rnn (e 12,840).

C H O Calc.ed C 81.50; H 10.75

Found C 81.27; H 10.77.

EXAMPLE 8 2,6,6-Trimethyl-1-[3-methyl-2-butenoyl]-1,3- cyclohexadiene Under anhydrous conditions 2,6,6-trimethyl-l-[3- methyl-2-butenoyl]-l-cyclohexene (2.1 g. )was heated to 4550 in the presence of N-bromosuccinimide (2.18 g.) in 20.4 ml. of CH C1 and 20.4 ml. of CCl,. The reaction mixture was allowed to react until complete precipitation of succinimide (1 h.).

Diethylamine (3.46 ml.) was added to the above mixture at 20 followed by 51 ml. of pet-ether (30-50). After filtration and evaporation (40) of the clear filtrate, the residual product was heated at 130150 in an atmosphere of argon during 1 h., and, after cooling, poured into, an excess of 10 HCl in the presence of pet.-ether and finally extracted with more pet-ether.

1.38 g. (66 ofa product with B.p. 70/0.001 Torr were obtained. This fraction was constituted by a 1:1 mixture of starting material and final product. Column chromatography (silicic ac. in the presence of benzene) gave a pure product:

1R: :1 1602, 1660 cm" MS: M+=204 NMR: 1.03 (6 H, s), 1.67 (3 H, s), 1.85 (3 H,d,J=ca. 1 cps), 2.02 (2 H,s), 6.01 (l H, s), 8 ppm. 

1. COMPOUNDS HAVING THE FORMULA
 2. Compounds according to claim 1 wherein the cycle comprises one double bond in position 2-.
 3. Compounds according to claim 1 wherein the cycle comprises one double bond in positIon 1-.
 4. Compounds according to claim 2 wherein R5, R6 and R7 represent hydrogen and R4 a lower alkyl radical.
 5. Compounds according to claim 2 wherein R4, R6 and R7 represent hydrogen and R5 a lower alkyl radical.
 6. Compounds according to claim 2 wherein R4, R5 and R7 represent hydrogen and R6 a lower alkyl radical.
 7. Compounds according to claim 2 wherein R4, R5 and R6 represent hydrogen and R7 a lower alkyl radical.
 8. Compounds according to claim 2 wherein R4, R5, R6 and R7 represent hydrogen, and wherein R1, R2 and R3 represent either hydrogen or one of them a lower alkyl radical, and the others hydrogen.
 9. Compounds according to claim 3 wherein R5, R6 and R7 represent hydrogen and R4 a lower alkyl radical.
 10. Compounds according to claim 3 wherein R4, R6 and R7 represent hydrogen and R5 a lower alkyl radical.
 11. Compounds according to claim 3 wherein R4, R5 and R7 represent hydrogen and R6 a lower alkyl radical.
 12. Compounds according to claim 3 wherein R4, R5 and R6 represent hydrogen and R7 a lower alkyl radical.
 13. Compounds according to claim 3 wherein R4, R5, R6 and R7 represent hydrogen, and wherein R1, R2 and R3 represent either hydrogen or one of them a lower alkyl radical and the others hydrogen. 